No abstract

Various adjuvant effects on the immunogenicity of the candidate inactivated Puumala virus vaccine were detected in BALB/c mice. Adjuvants under study were: aluminum hydroxide, spherical particles of Tobacco mosaic virus coat protein, B subunit of heat-labile enterotoxin of Escherichia coli, and low endotoxic lipopolysaccharide of Shigella sonnei. Aluminum hydroxide (1 mg/ml) did not affect neutralizing antibodies' induction and vaccine stability during storage compared to immunization with the vaccine without adjuvant. B subunit of heat-labile enterotoxin (0.2 µg/ml), low endotoxic lipopolysaccharide (50 µg/ml), and plant virus-based spherical particles (300 µg/ml) significantly enhance the humoral immune response of vaccine (p < 0.0001). Pronounced stimulation of IL-12 and IFN-ɣ was observed when mice were immunized with vaccines both with adjuvants (except of aluminum hydroxide) and without adjuvants. It has been shown that low endotoxic lipopolysaccharide contributes not only to enhance the immune response but also to stabilize vaccine immunogenicity during at least 1 year storage.

The full structure of the lipopolysaccharide core of bacteria Shigella flexneri types 2a and 5b, the causative agents of bacillary dysentery (shigellosis), was established by chemical methods, high-resolution electrospray ionization mass spectrometry, and two-dimensional NMR spectroscopy. The structure of the O-antigen repeating unit and the configuration and position of the linkage between the O-antigen and the core were determined in the lipopolysaccharide of S. flexneri type 2a.

Федеральное государственное бюджетное учреждение «Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства», 197022, г. Санкт-Петербург, Российская Федерация 2 Общество с ограниченной ответственностью «ГРИТВАК», 115522, г. Москва, Российская Федерация 3 Федеральное государственное бюджетное образовательное учреждение дополнительного профессионального образования «Российская медицинская академия непрерывного профессионального образования» Министерства здравоохранения Российской Федерации, 125993, г. Москва, Российская Федерация

Ïðîâåäåíî èññëåäîâàíèå òîëåðîãåííûõ ñâîéñòâ íîâîãî àïèðîãåííîãî, íèçêîýíäîòîêñè÷-íîãî êîìïëåêñíîãî ïðåïàðàòà íà îñíîâå áèîïîëèìåðîâ óãëåâîäíîé ïðèðîäû Shigella sonnei íà D-ãàëàêòîçàìèíîâîé è ïðÿìîé ìîäåëÿõ ýíäîòîêñè÷åñêîãî øîêà. Ïðîôèëàêòè÷åñêîå ââåäå-íèå ïðåïàðàòà çàùèùàåò ìûøåé (CBA ½ C57Bl/6)F1 îò ãèáåëè ïðè ââåäåíèè ëåòàëüíûõ äîç ýíäîòîêñèíà E. coli Î:55. Íà ïðÿìîé ìîäåëè ýíäîòîêñè÷åñêîãî øîêà áûëî ïîêàçàíî, ÷òî ïî-âûøåíèå äîçû èììóíèçàöèè êîððåëèðóåò ñ óâåëè÷åíèåì âûaeèâàåìîñòè è ñíèaeåíèåì óðîâíÿ ÔÍÎ-a â ñûâîðîòêàõ êðîâè ýêñïåðèìåíòàëüíûõ aeèâîòíûõ.Êëþ÷åâûå ñëîâà : ýíäîòîêñè÷eñêèé øîê, ýêçîïîëèñàõàðèä, ëèïîïîëèñàõàðèä, Shigella sonnei, ýíäîòîêñè÷eñêàÿ òîëåðàíòíîñòü, ÔÍÎ-. Ñåïñèñ, îáóñëîâëåííûé äåéñòâèåì ãðàìîòðèöà-òåëüíûõ áàêòåðèé, ÿâëÿåòñÿ îäíîé èç ïðè÷èí ðàçâè-òèÿ ñåðüåçíûõ îñëîaeíåíèé ïðè õèðóðãè÷åñêèõ âìå-øàòåëüñòâàõ, à òàêaeå ïðè òðàâìàõ è îaeîãàõ. Íåñìîòðÿ íà ïðèìåíåíèå àíòèáèîòèêîâ ïîñëåäíåãî ïîêîëåíèÿ, îáëàäàþùèõ øèðîêèì ñïåêòðîì äåéñòâèÿ, è âûñîêî-òåõíîëîãè÷íûõ ìåòîäîâ ëå÷åíèÿ ñåïñèñ îñòàåòñÿ ïà-òîëîãè÷åñêèì ñîñòîÿíèåì, àññîöèèðîâàííûì ñ âûñî-êèì óðîâíåì ëåòàëüíîñòè, êîòîðàÿ ïðè ñåïòè÷åñêîì (ýíäîòîêñè÷åñêîì) øîêå äîñòèãàåò 50% [1]. Íåýôôåê-òèâíîñòü èììóíîòåðàïèè íà ôîíå ñåïòè÷åñêèõ ñîñòî-ÿíèé è ïðè õèðóðãè÷åñêèõ âìåøàòåëüñòâàõ äèêòóåò íåîáõîäèìîñòü ðàçðàáîòêè íîâûõ ïîäõîäîâ íå òîëüêî ê ëå÷åíèþ ñåïñèñà, íî è ê ïðåäîòâðàùåíèþ, ïðîôè-ëàêòèêå, ïîäãîòîâêå ïàöèåíòà ê âîçìîaeíîìó ñåïòè-÷åñêîìó ñîñòîÿíèþ.Ýíäîòîêñè÷åñêèé øîê ðàçâèâàåòñÿ ïðè ïîïàäà-íèè áàêòåðèàëüíîãî ýíäîòîêñèíà (ëèïîïîëèñàõàðèäà, ËÏÑ) -êîìïîíåíòà êëåòî÷íîé ñòåíêè ãðàìîòðèöà-òåëüíûõ áàêòåðèé -â îðãàíèçì â ÷èñòîì âèäå, äå-ñòðóêòèâíàÿ ðîëü êîòîðîãî çàêëþ÷àåòñÿ â ìàññèðî-âàííîé âûðàáîòêå ïðîâîñïàëèòåëüíûõ öèòîêèíîâ, ïðåaeäå âñåãî ÔÍÎ-a è ÈË-1b [2,3]. Èõ ÷ðåçìåðíàÿ ïðîäóêöèÿ îáóñëîâëèâàåò çàïóñê ïàòîëîãè÷åñêèõ ïðî-öåññîâ, õàðàêòåðíûõ äëÿ ñåïñèñà: ãåíåðàëèçàöèÿ âîñ-ïàëåíèÿ, ïîâðåaeäåíèå ýíäîòåëèÿ ñîñóäîâ, àêòèâàöèÿ êîàãóëÿöèè è ñíèaeåíèå ôèáðèíîëèçà. Ýòè íàðóøå-íèÿ ìîãóò ïðèâåñòè ê ðàçâèòèþ ñèíäðîìà äèññåìè-íèðîâàííîãî âíóòðèñîñóäèñòîãî ñâåðòûâàíèÿ êðîâè, ãèïîêñèè òêàíåé è, êàê ñëåäñòâèå, ê ïîâðåaeäåíèþ òêàíåé è îðãàííîé äèñôóíêöèè [4], êîòîðàÿ â ñîâî-êóïíîñòè ñ óñòîé÷èâîé ãèïîòåíçèåé ïðèâîäèò ê ðàç-âèòèþ ýíäîòîêñè÷åñêîãî (ñåïòè÷åñêîãî) øîêà. ïîñëåäíèå ãîäû áûëà ñôîðìóëèðîâàíà êîíöåï-öèÿ èììóíîïðîôèëàêòèêè ýíäîòîêñè÷åñêîãî øîêà, íàïðàâëåííàÿ íà ðàçðàáîòêó ïðîòèâîøîêîâûõ âàêöèí ñ èñïîëüçîâàíèåì áèîïîëèìåðîâ óãëåâîäíîé ïðèðîäû (ÁÓÏ), ïðèìåíåíèå êîòîðûõ ïîçâîëèò ñîçäàòü ðåôðàê-òåðíîñòü (óñòîé÷èâîñòü) îðãàíèçìà ê ïîñëåäóþùåìó ìàññèâíîìó ïîïàäàíèþ áàêòåðèàëüíîãî ýíäîòîêñèíà. Íåñìîòðÿ íà âàaeíîñòü ïðîáëåìû, êîëè÷åñòâî ðàáîò ïî ïðîôèëàêòèêå ýíäîòîêñè÷åñêîãî øîêà îãðàíè÷å-íî, òàê êàê ñâÿçàíî â òîì ÷èñëå è ñ èñïîëüçîâàíèåì ËÏÑ, óðîâåíü ýíäîòîêñè÷íîñòè êîòîðîãî íå ïîçâî-ëÿåò èñïîëüçîâàòü åãî â êëèíè÷åñêîé ïðàêòèêå [5]. íàñòîÿùåì èññëåäîâàíèè ìû ïðîâîäèëè îöåí-êó ïðèíöèïèàëüíîé âîçìîaeíîñòè êîððåêöèè ýíäî-òîêñè÷åñêîãî øîêà ïðè ïðîôèëàêòè÷åñêîé èììóíè-çàöèè ìûøåé (CBA ½ C57Bl/6)F1 íîâûì àïèðîãåííûì íèçêîýíäîòîêñè÷íûì êîìïëåêñíûì ïðåïàðàòîì íà îñíîâå ÁÓ...